The overall objective of the proposed research is to identify the sequence of metabolic reactions leading to hydrochloric acid secretion by the gastric mucosa. The research approach involves the use of non-destructive optical techniques to monitor intracellular reactions in the intact functioning tissue. The optical measurements are combined with more conventional techniques of respiration measurements and biochemical analyses to construct a sequence of reactions which occur during the onset and cessation of acid production. Current studies focus on the role of 3'5'-cyclic AMP as a mediator of stimulating agents, the role of oxidative metabolism in the secretory process and the mechanism of action of secretory inhibitors. Previous work on this project has given support to the hypothesis that various stimulating agents, e.g., histamine, theophylline and gastrin, act by increasing intracellular levels of cyclic AMP. The subsequent action of cyclic AMP appears to be a direct stimulation of oxidative metabolism, i.e., the metabolic stimulation is not dependent upon increased acid secretion, which by some unknown mechanism promotes an increase in acid secretion. The current proposal seeks to further test this hypothesis and to provide more detail as to the interactions between the various processes.